The initial photochemical reactions of psoralen sensitizers with nucleic acids will be investigated with flash photolysis, coordinated with measurements of the binding interactions using spectrophotometric and fluorescence techniques. The object is to delineate the role of binding interactions in promoting the Type I reactions of the psoralen with the substrate, compared with the Type II reactions leading to singlet oxygen generation. New procedures for generating the reactive oxygen intermediates are being developed, in order to clarify the role of singlet oxygen, superoxide, and hydroxyl radicals in photodynamic systems, including the Type II reactions of psoralen sensitizers. The results will be analyzed with a recently developed theory of the diffusional reactions of reactive intermediates generated in the external medium with large biological targets. The current investigations on the photodynamic inactivation of enzymes will be continued, emphasizing the identification of the reactive intermediates and the specificity of their reactions with amino acid residues in terms of the microstructure.